Diabetes mellitus, a disease in which the pancreas fails to produce insulin or cells fail to respond to insulin for cellular metabolism of glucose, is a world-wide public health problem in terms of loss of quality of life and corresponding cost of care. Diabetes of the type-2 variety is a component of the so-called metabolic syndrome, which is a constellation of conditions linked to diabetes including obesity, hyperlipidemia, hypertension, immune system dysregulation, insulin resistance, hyperglycemia, atherosclerosis, and a series of cardiovascular events linked to these conditions. Metabolic syndrome complications are the primary causes of cardiovascular mortality in patients with diabetes and associated underlying conditions.
Data from the Diabetes Control and Complications Trial (DCCT), reported in 1993, show that quality of life may significantly be improved for people with diabetes if good control of blood sugar (glucose) levels is maintained. The primary benefit shown in DCCT was reduced complications from diabetes in cardiovascular disease progression.
To meet the current clinical recommendations of testing glucose, the most widely used, reliable and accurate method is a direct assay for glucose in a small amount of, typically, venous blood. Patients with certain kinds of diabetes must perform these tests on multiple occasions in each day. Hand-held instruments, which measure the amount of glucose based on the interaction of glucose with reagents pre-deposited on test strips, are now widely available. Typically these instruments detect the amount of glucose in blood to plus or minus 20%, based on specific enzymatic reactions using microliter samples of blood.
To reduce pain and inconvenience of existing blood glucose monitoring devices, alternatives to blood glucose assays have been attempted. Breath testing for glucose has been implemented by condensation of exhaled breath with assay of the resulting condensate for glucose using sensitive laboratory instruments such as Mass Spectrometry. For a variety of reasons chiefly resulting from technical difficulties with the accurate measurement of the amount of breath actually involved in the production of condensate, there is no acceptable and available handheld, consumer friendly device to measure glucose concentrations in breath. Furthermore, current attempts at breath monitoring are not applied to other analytes. First, the concentrations of glucose in condensate of breath are below the sensitivity of the methods used in handheld meters for blood, such as electrochemistry and electroimpedance. So, it is not possible to sample breath with these single use test strip devices and read accurate breath glucose concentrations. Even if it became technically possible to measure glucose of 0.4 mmol in breath with a test strip, the measurement of condensed breath is subject to a great number of inaccuracies of breathing rate, temperature, electrolyte content and other aspects of breath itself that prevent this method from being applied successfully on a hand-held device used by consumers. Another challenge of breath condensate is the difficulty with reproducibly collecting each breath in an identical manner, and the varied amounts of free water that is found in breath samples of different patients. Those skilled in the art of exhaled breath condensate measurement correct the collected breath sample by measuring its chloride concentration and use the chloride concentration to correct the measured glucose concentration for the amount of breath actually collected and the amount of water in the breath. This method suffers from the additional challenges of assay of chloride in a timely manner and from the inaccuracy that occurs in both measurements from factors not controlled by adjusting the results for breath chloride concentration.
While the chemistry for these tests is considered reliable, and the manufacturers of the test strips have demonstrated good quality control within the FDA standard of +/−20%, current self-testing for glucose remains a conscious process in which the diabetic must elect to take a blood sample and do the assay protocol for the hand-held instrument of choice. The primary failure for diabetics to do frequent self-testing for blood glucose levels, as recommend by the conclusions of the DCCT, is the pain associated with obtaining blood samples on a frequent schedule as well as the inconvenience of this blood testing process, particularly in public places.
Another issue is the need for more sensitive assays for glucose. Unfortunately, sensitive methods such as enzyme-linked immunosorbent assays (ELISA) are not useful for glucose measurement because glucose is not immunogenic and therefore not amenable to immune antibody assays such as ELISA. So in order to measure glucose at concentrations of 0.4 mmol such as found in breath, it is heretofore been necessary to collect condensate from a large amount of breath in a precise laboratory environment and to employ a sensitive laboratory assay method such as mass spectrometry. There are long time intervals spent waiting for testing results from laboratories that use methods such as mass spectrometry. Comparatively, blood testing by finger stick yields the results in 7 to 10 seconds even if there are disadvantages in accuracy.
Thus, there is a need for frequent and accurate self-testing of glucose to extend the life and expand the well-being of these patients. There is also a need to test other associated conditions of metabolic syndrome by means of analyte monitoring in breath. While efforts have been undertaken to increase the ease with which analytes from body fluids, such as glucose, can be periodically monitored, no proposed solution has proved entirely satisfactory that allows convenient monitoring with reduced pain and inconvenience.